Method for producing nanosurfaces with nano, micron, and/or submicron structures on a polymer

ABSTRACT

The present invention relates to a modified polymeric material. The modified polymeric material includes a polymer having a modified surface, where the modified surface includes nano, micron, and/or submicron scale features. The present invention also relates to an implant comprising the modified polymeric material. The present invention further relates to processes for making the modified polymeric material and the implant.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 15/066,747, filed with the U.S. Patent and Trademark Office of Mar.10, 2016, which is a continuation application of U.S. application Ser.No. 13/704,735, filed with the U.S. Patent and Trademark Office on Jul.25, 2013, which is a national stage filing under section 371 ofInternational Application No. PCT/US2011/041490, filed on Jun. 22, 2011,and published in English on Dec. 29, 2011 as WO 2011/163393, whichclaims the benefit of U.S. Provisional Patent Application Ser. No.61/358,851, filed Jun. 25, 2010. The entire disclosures of each of theprior applications are hereby incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates to a modified polymeric material. Thepresent invention also relates to an implant comprising the modifiedpolymeric material. The present invention further relates to processesfor making and using the modified polymeric material and the implant.

BACKGROUND OF THE INVENTION

There is an interest in the potential use of synthetic polymers and theeffect they may have on the design and function of hard and soft tissuerepair. To that end, various nanotechnology-based approaches have beentaken.

However, current methods for creating a surface roughness (e.g., at thesubmicron and micron level) are deficient in terms of scaling, cost,complexity, reagent acquisition, disposal, and accessibility,biocompatibility, and mechanical properties of the substrate.

Other deficiencies in the art of producing synthetic polymers havingrough surfaces at the nano, submicron, and micron level include, forexample, the following: (i) current methods to create nanosurfaceroughness on polymers are difficult in maintaining consistency acrossthe material type; (ii) current methods to create nanosurface roughnesson polymers use chemicals that are potentially toxic if such chemicalsare not completely removed; (iii) current methods to create nanosurfaceroughness on polymers use coating methods that can result indelamination of the polymer or added material and wear debris formation;(iv) current methods to create nanosurface roughness on polymers aredifficult to apply in three dimensions/outside of direct line of site;and (v) current methods have difficulty creating both porous voids andaspirities.

The present invention is directed to overcoming these and otherdeficiencies in the art.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a modified polymericmaterial, as described herein. In one embodiment, the modified polymericmaterial of the present invention includes a polymer having a modifiedsurface, where the modified surface includes nano, micron, and/orsubmicron scale features, including, but not limited to, pores, peaks,valleys, and ridges.

In another aspect, the present invention relates to an implant thatincludes a modified polymeric material, as described herein.

In a further aspect, the present invention relates to a process forpreparing a modified polymeric material, as described herein.

In one embodiment, the process involves providing a polymer, andsubjecting the polymer to a high vacuum treatment regimen underconditions effective to modify the surface of the polymer by introducingnano, micron, and/or submicron scale features to the surface of thepolymer. The high vacuum treatment regimen can include heating thepolymer at a high temperature, and then incubating the heat-treatedpolymer in a vacuum chamber under high vacuum conditions effective tomodify the surface of the polymer.

In another embodiment, the process involves providing a polymer, andincubating the polymer in mild heat in a vacuum chamber under highvacuum conditions effective to modify the surface of the polymer byintroducing nano, micron, and/or submicron scale features to the surfaceof the polymer.

In yet another embodiment, the process involves providing a polymer,treating the polymer with a chemical, enzyme, or other agent to softenthe surface, and then subjecting the polymer to vacuum conditionseffective to modify the surface of the polymer by introducing nano,micron, and/or submicron scale features to the surface of the polymer.

In yet another embodiment, the process involves providing a polymer, andincubating the polymer in methylene chloride, or other chemical,pharmaceutical, biologic agent, antibiotics, antimicrobial or bacterialstatic metals or other agents, growth factors, peptides, antibodies,viruses, RNAi, ceramic including but not limited to hydroxyapatite andcalcium phosphate in all size ranges, metal including but not limited totitanium, Ti6Al4V, or another polymer in a vacuum chamber under highvacuum conditions effective to modify the surface of the polymer byintroducing nano, micron, and/or submicron scale features to the surfaceof the polymer and coat or integrate the chemical, pharmaceutical,antibiotic, antimicrobial or bacterio-static metal or other agent,biologic agent, growth factors, peptides, antibodies, virus, RNAi,ceramic, metal or another polymer to the polymer.

Alternatively, the polymer could have the above agents in the polymerprior to the process.

In another aspect, the present invention relates to a modified polymericmaterial produced according to the processes described herein, as wellas to implants containing the modified polymeric material.

The present invention provides a robust method for producingnanosurfaces and nanosurfaces with nano, submicron, and micron scalefeatures on polymers, including nanosurfaced polyetheretherketone (PEEK)spine cages and nanosurfaced polypropylene hernia meshes, polymersutures and various polymers, including those used for implants,biomaterials, or drug delivery materials in any type of human or animaltissue.

The modified polymeric material of the present invention can be used forboth hard and soft tissue repair. In one aspect, the invention iseffective in developing nano-PEEK spine cages to treat spine repair andother applications that use PEEK polymer. Additionally, the inventionprovides nanosurfaced polypropylene hernia meshes. The invention furtherprovides an inexpensive and consistent process that creates ananosurface on polymers with a 2 or 3 dimensional geometry. The processof the present invention is useful in that it is easily scalable, doesnot use chemicals, and preserves the biocompatibility and mechanicalproperties of the substrate material. Furthermore the nanosurface of themodified polymeric material of the present invention can be useful inimproving or modifying biological responses, including protein orantibody adsorption, cell attachment, cell function, and subsequenttissue growth. The surface of the modified polymeric material of thepresent invention can also improve therapeutic attachment and deliveryof various attachments, including, for example, peptides, proteins,antibodies, drugs, metals, antimicrobial metals, biologic tissues oragents, stem cells, modified cells, and the like.

The present invention also provides PEEK and polypropylene surfaces thatmimic natural tissues, and that may be more bioactive and, thus, provideimproved hard and soft tissue integration markers compared toconventional PEEK and polypropylene surfaces. As mentioned, the presentinvention provides a nano to nano and micron rough surface.

With regard to biomedical uses, currently existing conventional PEEKmaterials to treat spine repair possess smooth material surfacefeatures. The same trend applies to polypropylene based materials thatare widely used in hernia repair applications. Therefore, nano roughsurface modification of such polymeric materials, as provided by thepresent invention, is a new paradigm for quick repair and surroundingtissue integration.

The present invention provides, in one aspect, a process for preparing amodified polymeric material using simultaneous heat and vacuum treatmenton PEEK polymeric material (without chemical process) to create nanorough surface without compromising the mechanical, physical and chemicalproperty of the polymer.

For polypropylene hernia meshes, the present invention provides, in oneaspect, a method that uses a high vacuum source in the presence ofpre-set mild heat or highly volatile methylene chloride treatment. Themethylene chloride has a very low boiling point (less than 40° C.; closeto body temperature heat) and can be removed spontaneously during thehigh vacuum treatment.

The present invention also relates to incorporating the process forpreparing a modified polymeric material into the PEEK manufacturingprocess. This modified process can be useful for creating a surface orpores in polymers (such as when the polymer is molded/extruded for thefirst time).

The present invention also relates to using the process for preparing amodified polymeric material to surfaces that are already modified orwill be modified thereafter. For example, the present inventioncontemplates using the modified process of the present invention to thetop of a previously modified surface, and also contemplates usinganother method (e.g., acid etching) to further modify the modifiedsurface after the process for preparing the modified polymeric materialto the surface is completed.

These and other objects, features, and advantages of this invention willbecome apparent from the following detailed description of the variousaspects of the invention taken in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating aspects of the present invention, thereare depicted in the drawings certain embodiments of the invention.However, the invention is not limited to the precise arrangements andinstrumentalities of the embodiments depicted in the drawings. Further,as provided, like reference numerals contained in the drawings are meantto identify similar or identical elements.

FIG. 1 is a schematic of one embodiment of the process of the presentinvention for preparing a modified polymeric material. In thisembodiment, the process produces a nano PEEK modified polymericmaterial.

FIG. 2 are SEM images of the surface of PEEK (plain) and of the surfaceof modified nano PEEK after treatment using one embodiment of theprocess of the present invention.

FIG. 3 are high magnification SEM images of the surface of PEEK (plain)and of the surface of a modified nano PEEK of the present invention.

FIG. 4 is an EDS spectra of nano and conventional PEEK.

FIG. 5 is a bar graph showing heat-plus-vacuum treated PEEK calciumdeposition data with osteoblast cells.

FIG. 6 are schematics of one embodiment of the process of preparing asurface modified nanopolypropylene of the present invention.

FIGS. 7A-7C are SEM images of a polypropylene mesh (plain) (FIG. 7A) andof polyproplyene meshes of the present invention having various nanofeatures. FIG. 7B shows an SEM image of the surface a nanopolypropylenemesh produced using methylene chloride treatment with high vacuum. FIGS.7C shows an SEM image of the surface a nanopolypropylene mesh producedusing pre-set heat with high vacuum.

FIG. 8 is a bar graph showing calcium deposition data with osteoblastcells for PEEK (untreated), nanoPEEK 1 (H₂SO₄ treated), and nanoPEEK 2(heated at 350° C. for 1 hour followed by vacuum) after 1 week, 2 weeks,and 3 weeks.

FIGS. 9A-9B are SEM images of the surface of modified nano PEEKmaterials produced according to one embodiment of the process ofpreparing a modified polymeric material of the present invention.

FIGS. 10A-10B are SEM images of the surface of modified nano PEEKmaterials produced according to one embodiment of the process ofpreparing a modified polymeric material of the present invention.

FIGS. 11A-11B are SEM images of the surface of modified nano PEEKmaterials produced according to one embodiment of the process ofpreparing a modified polymeric material of the present invention.

FIG. 12 is an SEM image of the surface of a modified nano PEEK materialproduced according to one embodiment of the process of preparing amodified polymeric material of the present invention.

FIGS. 13A-13B are SEM images of the surface of non-modified PEEKmaterials.

FIG. 14 is an SEM image of the surface of a non-modified PEEK material.

FIGS. 15A-15B are SEM images of the surface of a modified PEEK materialproduced using an embodiment of the process of the present inventioninvolving heating at 275° C. using a ramping protocol. Arrows indicatethe resemblance of the features (patterns) that were observed with 350°C. condition.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a modified polymeric material, asdescribed herein. In one embodiment, the modified polymeric material ofthe present invention includes a polymer having a modified surface,where the modified surface includes nano, micron, and/or submicron scalefeatures. In one embodiment, the nano, micron, and/or submicron scalefeatures can include, without limitation, surface features such aspores, peaks, valleys, and ridges.

A suitable polymer can include, without limitation, a thermoplasticpolymer. Examples of such thermoplastic polymers include polypropylene,polyetheretherketone (PEEK), poly lactic glycolic acid, poly lacticlactic acid, poly lactic acid, polyurethane, and the like. In oneembodiment, the polymer is in the form of a polymeric film. In otherembodiments, the polymer is in the form of a fiber, sphere, ovoid, rod,filament, monofilament, scaffold, plug, matrix, or the like.

The modified polymeric material of the present invention can beeffective to modify biological response (e.g., increased or decreasedtissue or bacteria attachment), fixation (e.g., improve mechanicalinterface with bone), or therapeutic attachment/delivery compared to acorresponding non-modified polymeric material.

The modified polymeric material of the present invention can beeffective to increase biological response or therapeuticattachment/delivery compared to a corresponding non-modified polymericmaterial. Examples of biological responses contemplated by the presentinvention include, without limitation, protein or antibody adsorption,cell attachment, cell function, tissue growth, and the like. Examples oftherapeutics contemplated by the present invention include, withoutlimitation, peptides, proteins, growth factors, antibodies, drugs,metals, antimicrobial metals, biologic tissues, biologic agents, stemcells, modified cells, and the like, including various others materialssuch as, but not limited to, various ceramics (e.g., HA, CP, etc.) andmetals (e.g., Ti, etc.).

The present invention further includes treating the modified polymericmaterial with a plasma treatment in an atmosphere including, but notlimited to, an oxygen atmosphere, plasma etching, oxygenation, or plasmaspraying with a ceramic, adding allograft, Demineralized bone matrix, orxenograft.

Therefore, in one embodiment, the modified polymeric material of thepresent invention can further include a functional attachment effectiveto increase biological response or therapeutic attachment/delivery. Thefunctional attachment can include, without limitation, a peptide,protein, growth factor, antibody, drug, metal, antimicrobial metal,biologic tissue, biologic agent, chemical agent, stem cell, modifiedcell, and the like.

In a further embodiment, the modified polymeric material of the presentinvention can further include: (i) a functional attachment effective toincrease biological response or therapeutic attachment/delivery; and/or(ii) a ceramic, metal, or another polymer integrated into the modifiedpolymeric material or coated onto the surface of the modified polymericmaterial.

The present invention also relates to an implant that includes amodified polymeric material, as described herein. In one embodiment, thethermoplastic polymer is polypropylene and the implant is a hernia meshor polymer suture. In another embodiment, the thermoplastic polymer isPEEK and the implant is a spine cage, vertebral body replacement, sutureanchor, dental implant, or maxillofacial implant, and the like.

The present invention further relates to a process for preparing amodified polymeric material, as described herein.

In one embodiment, the process involves: (i) providing a polymer; and(ii) subjecting the polymer to a high vacuum treatment regimen underconditions effective to modify the surface of the polymer by introducingnano, micron, and/or submicron scale features to the surface of thepolymer. In a particular embodiment of this process, the high vacuumtreatment regimen can include: (i) heating the polymer at a hightemperature; and (ii) incubating the heat-treated polymer in a vacuumchamber under high vacuum conditions effective to modify the surface ofthe polymer. The polymer used in this embodiment of the process of thepresent invention can include, without limitation, PEEK.

The heating can be at a heat range specific to the polymer and relativeto the polymer's melting and crystallization temperature. The incubatingcan be carried out for at least 5 hours.

In illustrative examples, the heating can be carried out at atemperature of greater than 400° C., between about 275° C. and about400° C., between about 300° C. and about 400° C., between about 325° C.and about 400° C., between about 350° C. and about 400° C., or betweenabout 375° C. and about 400° C. In a particular embodiment, the heatingcan be carried out at a temperature of about 350° C. for between about 1and about 90 minutes. The material can be heated and vacuum treatedsimultaneously. The heating and simultaneous high vacuum conditions aresuch as to be effective to modify the surface of the polymer inaccordance with the present invention. The temperature and vaccumpressure can be modified to create different surface features to achievethe desired biological response or other response or benefit.

In a variation of this embodiment, the high vacuum treatment regimen caninclude loading polymer samples at 150° C. and subjecting the polymer topump-down procedures to 10 mTorr (pump/purge sequences). Thereafter, thepolymer is subjected to a ramp-up period during which the temperature isincreased from about 150° C. to about 350° C. over the course ofapproximately 1 hour. The polymer is left at steady state for about 1hour (at 10 mTorr at 350° C.). The polymer is then subjected to aramp-down period during which the temperature is decreased to about 150°C. over the course of 1 hour. The sample is then extracted at 150° C.and transferred to a vacuum desiccator and stored under high vacuum forapproximately 8 hours.

In another embodiment, the process involves heating at 275° C. using aramping protocol, same as for 350° C. Other conditions of the processcan be the same, but the maximum temperature can be held at 275° C. for1 hour. Surface features of a modified polymeric material produced usingsuch process are shown in FIGS. 15A-15B. For example, as shown in FIGS.15A-15B, the SEM results provided a new type of surface feature in thiscondition. In particular, the topography is rougher but with less porousstructure compared to 350° C. treatment condition. Again thetopographical features were homogenous throughout the surface like the350° C. treatment.

In one aspect, the process of the present invention is effective toproduce a modified polymeric material that includes a polymer having amodified surface, where the modified surface includes micron and/orsubmicron scale features. In one embodiment, the polymer is athermoplastic polymer, where the thermoplastic polymer includes, but isnot limited to, polypropylene and polyetheretherketone (PEEK). In aparticular embodiment, the polymer is in the form of a polymeric film.In another embodiment, the modified polymeric material is effective toincrease biological response or therapeutic attachment/delivery comparedto a corresponding non-modified polymeric material. The biologicalresponse can include, without limitation, protein or antibodyadsorption, cell attachment, cell function, and tissue growth. Thetherapeutic can be, without limitation, a peptide, protein, growthfactor, antibody, drug, metal, antimicrobial metal, biologic tissue,biologic agent, chemical agent, stem cell, modified cell, and the like.Further, the modified polymeric material can further include afunctional attachment effective to increase biological response ortherapeutic attachment/delivery. Suitable functional attachments caninclude, without limitation, a peptide, protein, growth factor,antibody, drug, metal, antimicrobial metal, biologic tissue, biologicagent, chemical agent, stem cell, modified cell, and the like.

In one embodiment, the process of preparing a modified polymericmaterial can further include: (i) applying an acid etching procedureeither before or after the polymer is modified; and/or (ii)integrating/coating the modified polymeric material with hydroxyapatite,titanium, calcium phosphate, and/or the like to yield a two layer orintegration of the modified polymeric material and the hydroxyapatite,titanium, calcium phosphate, and the like.

In another embodiment, the process involves: (i) providing a polymer;and (ii) incubating the polymer in mild heat in a vacuum chamber underhigh vacuum conditions effective to modify the surface of the polymer byintroducing micron and/or submicron scale features to the surface of thepolymer. The polymer used in this embodiment of the process of thepresent invention can include, without limitation, polypropylene. Themild heat can be, without limitation, a temperature of not more thanabout 70° C. The incubating can be carried out for between about 18 and30 hours.

In yet another embodiment, the process involves: (i) providing apolymer; and (ii) incubating the polymer in methylene chloride in avacuum chamber under high vacuum conditions effective to modify thesurface of the polymer by introducing micron and/or submicron scalefeatures to the surface of the polymer. The polymer used in thisembodiment of the process of the present invention can include, withoutlimitation, polypropylene. The incubating can be carried out for betweenabout 18 and 30 hours.

In another aspect, the present invention relates to a modified polymericmaterial produced according to the processes described herein, as wellas to implants containing the modified polymeric material. In view ofthe present disclosure, one of ordinary skill in the art would readilybe able to prepare and use implants that contain or include the modifiedpolymeric material of the present invention.

In another aspect, the present invention relates to using the modifiedpolymeric material of the present invention as or combined with variousbiomaterials (e.g., scaffolds, bone void fillers, fusion materialsautograft, Demineralized bone graft, allograft, xenograft, and thelike), components, local and systemic drug delivery materials/polymers,and various other items suitable for being used or combined with themodified polymeric material.

In another aspect, the present invention provides a modified polymericmaterial that further includes two layer/integration aspects (e.g.,integrating/coating with hydroxyapatite, titanium, calcium phosphate).

One advantage of the present invention is the straight-forward creationof novel nanosurfaced polymers for spinal repair, spinal fusion, dentalimplants, biomaterials, suture anchors, and where other alternatives arenot possible, including in porous structures that are hard to reach withfluids or line of site methods. The method of the present inventioninvolves no chemical treatment or cumbersome coating technologiestraditionally used in polymer surface modifications that attempt tocreate a nano rough surface. The procedure of the present invention iseasy and cost effective, efficient for mass production; in particularthere will be no chemical residues and reduced particle debris. Further,no major bulk mechanical property will be changed since the processingtemperature involves is low compared to the melting temperature of thepolymer.

As noted herein, the present invention precludes the usage of chemicaltreatment, which is a concern that needs to be addressed in the contextof cytotoxicity. Also, conventionally used coating technologies (tocreate nano, micron, or submicron roughness) possibly producedelamination or wear debris, which results in the potential forcytotoxicity. The present invention also provides a method to create acustom nanosurface to drive desired protein/antibody adsorption and cellresponses. For example, this could be done by changing the processparameters to make a different nano and micron surfaces.

Provided below are further descriptions of certain aspects andembodiments of the present invention, some descriptions of whichreiterate or further explain various aspects and embodiments containedelsewhere herein.

In one embodiment, the process of the present invention involvesproviding a polymer, and subjecting the polymer to a high vacuumtreatment regimen under conditions effective to modify the surface ofthe polymer by introducing nano, micron, and/or submicron scale featuresto the surface of the polymer. The high vacuum treatment regimen caninclude heating the polymer at a high temperature, and then incubatingthe heat-treated polymer in a vacuum chamber under high vacuumconditions effective to modify the surface of the polymer.

In another embodiment, the process involves providing a polymer, andincubating the polymer in mild heat in a vacuum chamber under highvacuum conditions effective to modify the surface of the polymer byintroducing nano, micron, and/or submicron scale features to the surfaceof the polymer.

In yet another embodiment, the process involves providing a polymer,treating the polymer with a chemical, enzyme, or other agent to softenthe surface, and then subjecting the polymer to vacuum conditionseffective to modify the surface of the polymer by introducing nano,micron, and/or submicron scale features to the surface of the polymer.

In yet another embodiment, the process involves providing a polymer, andincubating the polymer in methylene chloride, or other chemical,pharmaceutical, biologic agent, antibiotics, antimicrobial or bacterialstatic metals or other agents, growth factors, peptides, antibodies,viruses, RNAi, ceramic including but not limited to hydroxyapatite andcalcium phosphate in all size ranges, metal including but not limited totitanium, Ti6Al4V, or another polymer in a vacuum chamber under highvacuum conditions effective to modify the surface of the polymer byintroducing nano, micron, and/or submicron scale features to the surfaceof the polymer and coat or integrate the chemical, pharmaceutical,antibiotic, antimicrobial or bacterio-static metal or other agent,biologic agent, growth factors, peptides, antibodies, virus, RNAi,ceramic, metal or another polymer to the polymer.

Alternatively, the polymer could have the above agents in the polymerprior to the process.

In another aspect, the present invention relates to a modified polymericmaterial produced according to the processes described herein, as wellas to implants containing the modified polymeric material.

The present invention provides a robust method for producingnanosurfaces and nanosurfaces with nano, submicron, and micron scalefeatures on polymers, including nanosurfaced polyetheretherketone (PEEK)spine cages and nanosurfaced polypropylene hernia meshes, polymersutures and various polymers, including those used for implants,biomaterials, or drug delivery materials in any type of human or animaltissue.

The modified polymeric material of the present invention can be used forboth hard and soft tissue repair. In one aspect, the invention iseffective in developing nano-PEEK spine cages to treat spine repair andother applications that use PEEK polymer. Additionally, the inventionprovides nanosurfaced polypropylene hernia meshes. The invention furtherprovides an inexpensive and consistent process that creates ananosurface on polymers with a 2 or 3 dimensional geometry. The processof the present invention is useful in that it is easily scalable, doesnot use chemicals, and preserves the biocompatibility and mechanicalproperties of the substrate material. Furthermore the nanosurface of themodified polymeric material of the present invention can be useful inimproving or modifying biological responses, including protein orantibody adsorption, cell attachment, cell function, and subsequenttissue growth. The surface of the modified polymeric material of thepresent invention can also improve therapeutic attachment and deliveryof various attachments, including, for example, peptides, proteins,antibodies, drugs, metals, antimicrobial metals, biologic tissues oragents, stem cells, modified cells, and the like.

The present invention also provides PEEK and polypropylene surfaces thatmimic natural tissues, and that may be more bioactive and, thus, provideimproved hard and soft tissue integration markers compared toconventional PEEK and polypropylene surfaces. As mentioned, the presentinvention provides a nano to nano and micron rough surface.

With regard to biomedical uses, currently existing conventional PEEKmaterials to treat spine repair possess smooth material surfacefeatures. The same trend applies to polypropylene based materials thatare widely used in hernia repair applications. Therefore, nano roughsurface modification of such polymeric materials, as provided by thepresent invention, is a new paradigm for quick repair and surroundingtissue integration.

The present invention provides, in one aspect, a process for preparing amodified polymeric material using simultaneous heat and vacuum treatmenton PEEK polymeric material (without chemical process) to create nanorough surface without compromising the mechanical, physical and chemicalproperty of the polymer.

For polypropylene hernia meshes, the present invention provides, in oneaspect, a method that uses a high vacuum source in the presence ofpre-set mild heat or highly volatile methylene chloride treatment. Themethylene chloride has a very low boiling point (less than 40° C.; closeto body temperature heat) and can be removed spontaneously during thehigh vacuum treatment.

The present invention also relates to incorporating the process forpreparing a modified polymeric material into the PEEK manufacturingprocess. This modified process can be useful for creating a surface orpores in polymers (such as when the polymer is molded/extruded for thefirst time).

The present invention also relates to using the process for preparing amodified polymeric material to surfaces that are already modified orwill be modified thereafter. For example, the present inventioncontemplates using the modified process of the present invention to thetop of a previously modified surface, and also contemplates usinganother method (e.g., acid etching) to further modify the modifiedsurface after the process for preparing the modified polymeric materialto the surface is completed.

EXAMPLES

The following examples are intended to illustrate particular embodimentsof the present invention, but are by no means intended to limit thescope of the present invention.

Example 1 Nano PEEK Spine Cages

As provided by the present invention, research and testing has produceda nano surfaced PEEK without any chemical treatment, but using highvacuum (in the range of 10⁻² Torr to 10⁻⁶ Torr) and a temperature of350° C. at 15 min, 30 min, 60 min. The surface is novel and theprocessing method is novel.

FIG. 1 is a schematic of one embodiment of the nano PEEK preparationmethod of the present invention. For example, PEEK coupons were kept inthe pre-heated (at 350° C.) heating oven for 15, 30, 60 min,respectively. Ceramic plates were used to keep the coupons. After theabove prescribed times, the samples were immediately transferred to avacuum chamber and high vacuum was applied for 8 hours. Vacuum wasreleased slowly and the PEEK samples were characterized further. SEManalysis (see FIGS. 2-3) and contact angle analysis experiments wereperformed and confirmed the nano features on the modified surfaces andchanged contact angle values. Initial in vitro osteoblast cell dataprovided information that increased cell function on samples treated at60 min compared to other timing points and plain PEEK samples. EDSspectra data was plain and nano PEEK samples (see FIG. 4). EDS datarevealed that PEEK surface before and after treatment showed the samespectrum, indicating that there is no change in chemistry by the nanotreatment process.

Calcium deposition studies with osteoblast cell showed that treated PEEKdisplayed significantly higher calcium after 1 w, 2 w, and 3 w, althoughpercentage of increase decreased with time (see FIG. 5).

Example 2 Nano Polypropylene Hernia Mesh

As provided by the present invention, research and testing has producedtwo different novel nano surfaced polypropylene based hernia meshscaffolds without any harsh chemicals (acids and bases). For example,one approach used mild, easily removable methylene chloride incombination with high vacuum (in the range of 10⁻² Torr to 10⁻⁶ Torr).Additionally, a second nanorough surface was produced on the polymerscaffolds at the same high vacuum condition using a temperature of 60°C. without any chemical treatment. Both surfaces are novel and theprocessing methods are novel.

The surface of the polymer scaffold is processed at high vacuum(typically around at 10⁻⁶ Torr) with pre-set mild heat (at 60° C.) orwith methylene chloride treatment without heat treatment for 24 hours(see FIG. 6). For the treated samples, polymer scaffolds were graduallybrought down to atmospheric pressure and temperature.

To look for the surface difference between the samples due to theprocess illustrated in the depiction, Scanning Electron Microscope (SEM)images were obtained using FEI NOVA nanoSEM FESEM (FEI, Hillsboro,Oreg.) using low/high vacuum using through the lens (TLD) secondaryelectron detector using low to high magnification (10-200 k). Polymerscaffolds were mounted on copper tape using silver paste for additionalconductivity. They were coated with Pt for 60 sec prior to imaging.

Accumulated charge from the electron beam was a problem but was reduceddue to the better conductivity provided by embedding the mesh in silverpaste.

Fine nano surface features were evident under above SEM condition fortreated samples compared plain samples (see FIG. 7). The difference inthe nanorough pattern reflects the two different processes used withsame polymer scaffold.

Therefore, the present invention is effective to produce at least twodifferent nanoroughness patterns on the same polymer using a high vacuumprocess with pre-set mild heat treatment and with methylyne chloridetreatment.

Example 3 Calcium Deposition Results Using Osteoblast Cells

Calcium deposition studies with osteoblast cells were conducted forvarious embodiments of the process of preparing modified polymericmaterials having micron and submicron surface roughness. In particular,calcium deposition studies were conducted using PEEK nanosurfaced using(i) a sulfuric acid etching technique (PEEK 1) and (ii) a heat plus highvacuum technique (PEEK 2), as described herein.

FIG. 8 illustrates the calcium deposition/osteoblast cell results PEEK(untreated), nanoPEEK 1 (H₂SO₄ treated), nanoPEEK 2 (heated at 350° C.for 1 hour, followed by vacuum), and glass after 1 w, 2 w, and 3 w.

Increased osteoblast adhesion correlates to enhanced cell-to-cellcontact which can promote osteoblast differentiation to calciumdepositing cells. Compared to untreated PEEK, this study providedevidence of enhanced Ca deposition on both treated PEEK after 3 weeks.While Ca deposition by both treated PEEK was not different from glasssurface, it was significantly greater compared to plain PEEK surface.There are many possible reasons why Ca deposition may be enhanced onthese nano PEEK materials, particularly with the invented nano-featuredsurfaces. Specifically, compared to plain PEEK materials, nano PEEKmaterials have greater surface areas and consequently higher numbers ofatoms at their surfaces.

Example 4 Nanosurfacing of Polymers Using Heat with Simultaneous Vacuum

As discussed elsewhere herein, in one aspect, the present inventionrelates to a process for preparing a modified polymeric material.Research was conducted on a particular embodiment of this process(described below), where the process generally involved subjectingpolymers (targeted for nanosurfacing) to heat with simultaneous vacuum.

In this example, the high vacuum treatment regimen included loadingpolymer samples (i.e., PEEK) at 150° C. and subjecting the polymer topump-down procedures to 10 mTorr (pump/purge sequences). Thereafter, thepolymer was subjected to a ramp-up period during which the temperaturewas increased from about 150° C. to about 350° C. over the course ofapproximately 1 hour. The polymer was left at steady state for about 1hour (at 10 mTorr at 350° C.). The polymer was then subjected to aramp-down period during which the temperature was decreased to about150° C. over the course of 1 hour. The sample was then extracted at 150°C. and transferred to a vacuum desiccator and stored under high vacuumfor approximately 8 hours.

Results of the polymer nanosurfaces produced by this process are shownin the SEM images of FIGS. 9-12 and 15, as compared to “plain” polymersurfaces as shown in the SEM images of FIGS. 13-14.

Although preferred embodiments have been depicted and described indetail herein, it will be apparent to those skilled in the relevant artthat various modifications, additions, substitutions, and the like canbe made without departing from the spirit of the invention and these aretherefore considered to be within the scope of the invention as definedin the claims which follow.

What is claimed is:
 1. A modified polymeric material comprising apolymer having a modified surface, wherein said modified surfacecomprises nano, micron, and/or submicron scale features.
 2. The modifiedpolymeric material according to claim 1, wherein the polymer is athermoplastic polymer.
 3. The modified polymeric material according toclaim 2, wherein the thermoplastic polymer is selected from the groupconsisting of polypropylene, polyetheretherketone (PEEK), poly lacticglycolic acid, poly lactic lactic acid, poly lactic acid, polyurethane,and the like.
 4. The modified polymeric material according to claim 1,wherein the polymer is in the form of a polymeric film, fiber, sphere,ovoid, rod, filament, monofilament, or scaffold, plug, or matrix.
 5. Themodified polymeric material according to claim 1, wherein said modifiedpolymeric material is effective to modify biological response (e.g.,increased or decreased tissue or bacteria attachment), fixation (e.g.,improve mechanical interface with bone), or therapeuticattachment/delivery compared to a corresponding non-modified polymericmaterial.
 6. The modified polymeric material according to claim 5,wherein the biological response is selected from the group consisting ofprotein or antibody adsorption, cell attachment, cell function, andtissue growth.
 7. The modified polymeric material according to claim 5,wherein the therapeutic is selected from the group consisting of apeptide, protein, growth factor, antibody, drug, metal, antimicrobialmetal, biologic tissue, biologic agent, chemical agent, stem cell,modified cell, and the like.
 8. The modified polymeric materialaccording to claim 1 further comprising: a functional attachmenteffective to increase biological response or therapeuticattachment/delivery; and/or a ceramic, metal, or another polymerintegrated into the modified polymeric material or coated onto thesurface of the modified polymeric material.
 9. The modified polymericmaterial according to claim 8, wherein the functional attachment isselected from the group consisting of a peptide, protein, growth factor,antibody, drug, metal, antimicrobial metal, biologic tissue, biologicagent, chemical agent, stem cell, modified cell, and the like.
 10. Animplant comprising: a modified polymeric material according to claim 1.11. The implant according to claim 10, wherein the polymer ispolypropylene and the implant is a hernia mesh or polymer suture. 12.The implant according to claim 10, wherein the polymer is PEEK and theimplant is a spine cage, vertebral body replacement, suture anchor,dental implant, maxillofacial implant, or the like.
 13. A process forpreparing a modified polymeric material, said process comprising:providing a polymer; and subjecting the polymer to a high vacuumtreatment regimen under conditions effective to modify the surface ofthe polymer by introducing nano, micron, and/or submicron scale featuresto the surface of the polymer.
 14. The process according to claim 13,wherein the high vacuum treatment regimen comprises: heating the polymerat a high temperature; and/or incubating the heat-treated polymer in avacuum chamber under high vacuum conditions effective to modify thesurface of the polymer, wherein said heating can be at a heat rangespecific to the polymer and relative to the polymer's melting andcrystallization temperature.
 15. The process according to claim 14,wherein said heating is carried out at a temperature of between about300° C. and about 400° C.
 16. The process according to claim 14, whereinsaid heating is carried out at a temperature of about 350° C. forbetween about 1 and about 90 minutes.
 17. The process according to claim13, wherein said incubating is carried out for at least 5 hours.
 18. Theprocess according to claim 13, wherein the high vacuum treatment regimencomprises: subjecting the polymer to heating and simultaneous highvacuum conditions effective to modify the surface of the polymer. 19.The process according to claim 18, wherein said subjecting comprises:(a) loading the polymer at a temperature of about 150° C.; (b) applyinghigh vacuum conditions of about 10 mTorr; (c) increasing the temperatureto about 350° C. over the course of about 1 hour; (d) maintaining thepolymer at about 350° C. at 10 mTorr for about 1 hour; (e) decreasingthe temperature to about 150° C. over the course of about 1 hour; and(f) extracting the polymer at about 150° C.
 20. The process according toclaim 19 further comprising: storing the extracted polymer under highvacuum conditions for about 8 hours.
 21. A process for preparing amodified polymeric material, said process comprising: providing apolymer; and incubating the polymer in mild heat in a vacuum chamberunder high vacuum conditions effective to modify the surface of thepolymer by introducing nano, micron, and/or submicron scale features tothe surface of the polymer.
 22. The process according to claim 21,wherein said mild heat comprises a temperature of not more than 70° C.23. The process according to claim 21, wherein said incubating iscarried out for between about 18 and 30 hours.
 24. A process forpreparing a modified polymeric material, said process comprising:providing a polymer; and incubating the polymer in methylene chloride ina vacuum chamber under high vacuum conditions effective to modify thesurface of the polymer by introducing micron and/or submicron scalefeatures to the surface of the polymer.
 25. The process according toclaim 24, wherein said incubating is carried out for between about 18and 30 hours.
 26. The process according to claim 13 further comprising:applying an acid etching procedure either before or after the polymer ismodified; and/or integrating/coating the modified polymeric materialwith hydroxyapatite, titanium, calcium phosphate, and/or the like toyield a two layer or integration of the modified polymeric material andthe hydroxyapatite, titanium, calcium phosphate, and the like.
 27. Theprocess according to claim 13, wherein the polymer is a thermoplasticpolymer.
 28. The process according to claim 27, wherein thethermoplastic polymer is selected from the group consisting ofpolypropylene, polyetheretherketone (PEEK), poly lactic glycolic acid,poly lactic lactic acid, poly lactic acid, polyurethane, and the like.29. The process according to claim 13, wherein the polymer is in theform of a polymeric film, fiber, sphere, ovoid, rod, filament,monofilament, or scaffold, plug, or matrix.
 30. The process according toclaim 13, wherein said modified polymeric material is effective tomodify biological response (e.g., increased or decreased tissue orbacteria attachment), fixation (e.g., improve mechanical interface withbone), or therapeutic attachment/delivery compared to a correspondingnon-modified polymeric material.
 31. The process according to claim 30,wherein the biological response is selected from the group consisting ofprotein or antibody adsorption, cell attachment, cell function, andtissue growth.
 32. The process according to claim 30, wherein thetherapeutic is selected from the group consisting of a peptide, protein,growth factor, antibody, drug, metal, antimicrobial metal, biologictissue, biologic agent, chemical agent, stem cell, modified cell, andthe like.
 33. The process according to claim 13 further comprising: afunctional attachment effective to increase biological response ortherapeutic attachment/delivery; and/or a ceramic, metal, or anotherpolymer integrated into the modified polymeric material or coated ontothe surface of the modified polymeric material.
 34. The processaccording to claim 33, wherein the functional attachment is selectedfrom the group consisting of a peptide, protein, growth factor,antibody, drug, metal, antimicrobial metal, biologic tissue, biologicagent, chemical agent, stem cell, modified cell, and the like.
 35. Amodified polymeric material produced by the process according to claim13.
 36. A modified polymeric material according to claim 35, whereinsaid modified polymeric material can be used as, used with, or combinedwith biomaterials (e.g., scaffolds, bone void fillers, fusion materialsautograft, Demineralized bone graft, allograft, xenograft, and thelike), components, local and systemic drug delivery materials/polymers,and various other items suitable for being used or combined with themodified polymeric material.
 37. A modified polymeric material accordingto claim 35, wherein said modified polymeric material further includestwo layer/integration aspects (e.g., integrating/coating withhydroxyapatite, titanium, calcium phosphate).
 38. An implant comprisinga modified polymeric material produced according to the process of claim13.